“Understanding how tuberculosis-associated microenvironment renders the human macrophage susceptible to HIV-1: a perspective on metabolism and cell activation"
The LIA IM-TB/HIV #1167 is a “without borders” laboratory created for a 4-year period (2017-2020) between two groups of the IPBS headed by Dr. O. Neyrolles and Dr. I. Maridonneau-Parini, and the “Laboratorio de Inmunología de Enfermedades Respiratorias” led by Dr. MDC. Sasiain and Dr. L. Balboa at the IMEX CONICET- Academia Nacional de Medicina of Buenos Aires (Argentina).
The LIA consists of 7 researchers (Lugo-Villarino G., Verollet C., Raynaud-Messina B., Maridonneau-Parini I., and Neyrolles O. in France; Balboa L. and Sasiain MDC. in Argentina), and multiple PhD students and post-doctoral fellows (Dupont M. and Souriant S. in France; Genoula M., Marín Franco JL., Duette G. and Kviatcovsky D. in Argentina). It receives the support from the CNRS, the University Toulouse III-Paul Sabatier, the ECOS-SUD program, the CONICET/IMEX and the Argentinean National Agency of Promotion of Science and Technology. The French Co-coordinators are Dr. Christel Vérollet and Dr. Geanncarlo Lugo-Villarino, and the Argentinian Coordinator is Dr. Luciana Balboa).
This LIA takes place in a co-infection context, where Tuberculosis (TB) and acquired immune deficiency syndrome (AIDS) are among the deadliest diseases due to a single infectious agent. The well-known synergy between the two pathogens responsible for these diseases, Mycobacterium tuberculosis (Mtb) and HIV-1, respectively, places an immense burden in the health care systems in resource-limited countries where co-infection with these pathogens is prevalent, but also a serious public health issue in South American and European countries. For these reasons, there is an urgent need for fundamental science to drive innovations for improving TB/HIV care and control, and for fundamental research, to improve our understanding of the interaction of these two pathogens within the human host.
It is widely accepted that the depletion of CD4+ T cells, the hallmark of AIDS, is likely to be the main contributing factor to the susceptibility to TB in co-infected patients, as these lymphocytes are essential to control Mtb. However, while it is well known that viral load is higher in anatomical sites where co-infection occurs with Mtb, the mechanisms responsible for the exacerbation of HIV-1 infection in the presence of the bacilli are not fully understood. In this context, the implication of macrophages, which are major host cell reservoir for both Mtb and HIV-1, is suspected to be crucial.
It is precisely the latter point that gives rise to the central theme for this LIA project: the exacerbation of HIV-1 infection is driven by Mtb by causing a shift in the activation and metabolic state of macrophages, a condition that ultimately renders these cells more permissible and/or create a more favorable environment for HIV replication. Indeed, this LIA consortium is already experiencing quite a success in terms of: i) increasing the synergy and equilibrium between all teams and personnel involved, ii) creating a dynamic pipeline between the scientific aims shared by French and Argentinian teams, iii) producing quality scientific output in terms of publications in peer-review international journals, and iv) gaining visibility with the international, national and local news media. It is expected that the scientists responsible for this LIA consortium will apply renewal for the next 4-yr period (2021-25), inferring a long and fruitful fundamental research that ultimately improves our understanding of the interaction of Mtb and HIV-1 with the human host.
List of publications crediting the LIA:
- “Tuberculosis exacerbates HIV-1 infection through IL-10/STAT3-dependent tunneling nanotube formation in macrophages" Souriant S, Balboa L, Pingris K, Kviatcovsky D, Cougoule C, Lastrucci C, Bah A, Gasser R, Poincloux R, Raynaud-Messina B, Al Saati T, Inwentarz S, Poggi S, Moraña EJ, Gonzalez-Montaner P, Corti M, Lagane B, Vergne I, Allers C, Kaushal D, Kuroda MJ, Sasiain MDC, Neyrolles O, Maridonneau-Parini I, Lugo-Villarino G, Vérollet C. Cell Rep. 2019 Mar 26;26(13):3586-3599.e7. doi: 10.1016/j.celrep.2019.02.091.
- "Effect of the BTK inhibitor ibrutinib on macrophage- and γδ T cell-mediated response against Mycobacterium tuberculosis." Colado A, Genoula M, Cougoule C, Marín Franco JL, Almejún MB, Risnik D, Kviatcovsky D, Podaza E, Elías EE, Fuentes F, Maridonneau-Parini I, Bezares FR, Fernandez Grecco H, Cabrejo M, Jancic C, Sasiain MDC, Giordano M, Gamberale R, Balboa L, Borge M. Blood Cancer J. 2018 Nov 5;8(11):100. doi: 10.1038/s41408-018-0136
- "B Cells Producing Type I IFN Modulate Macrophage Polarization in Tuberculosis." Bénard A, Sakwa I, Schierloh P, Colom A, Mercier I, Tailleux L, Jouneau L, Boudinot P, Al-Saati T, Lang R, Rehwinkel J, Loxton AG, Kaufmann SHE, Anton-Leberre V, O'Garra A, Sasiain MDC, Gicquel B, Fillatreau S, Neyrolles O, Hudrisier D. Am J Respir Crit Care Med. 2018 Mar 15;197(6):801-813. doi: 10.1164/rccm.201707-1475O
- "The C-Type Lectin Receptor DC-SIGN Has an Anti-Inflammatory Role in Human M(IL-4) Macrophages in Response to Mycobacterium tuberculosis." Lugo-Villarino G, Troegeler A, Balboa L, Lastrucci C, Duval C, Mercier I, Bénard A, Capilla F, Al Saati T, Poincloux R, Kondova I, Verreck FAW, Cougoule C, Maridonneau-Parini I, Sasiain MDC, Neyrolles O. Front Immunol. 2018 Jun 12;9:1123. doi: 10.3389/fimmu.2018.01123
- "Formation of Foamy Macrophages by Tuberculous Pleural Effusions Is Triggered by the Interleukin-10/Signal Transducer and Activator of Transcription 3 Axis through ACAT Upregulation." Genoula M, Marín Franco JL, Dupont M, Kviatcovsky D, Milillo A, Schierloh P, Moraña EJ, Poggi S, Palmero D, Mata-Espinosa D, González-Domínguez E, León Contreras JC, Barrionuevo P, Rearte B, Córdoba Moreno MO, Fontanals A, Crotta Asis A, Gago G, Cougoule C, Neyrolles O, Maridonneau-Parini I, Sánchez-Torres C, Hernández-Pando R, Vérollet C, Lugo-Villarino G, Sasiain MDC, Balboa L. Front Immunol. 2018 Mar 9;9:459. doi: 10.3389/fimmu.2018.00459
They talk about the LIA :
- Suisse Radio/TV, RST/CQFD, live radio interview on March 27th, 2019: « Pourquoi le virus du sida se multiplie plus vite chez une personne tuberculeuse » (in french)
- France 3 Occitanie, TV segment report on March 28th, 2019: « VIH et tuberculose : à Toulouse des chercheurs ont fait une découverte capitale » (in french)
- La Dépêche du Midi, article published on April 1st, 2019 : « Ils montrent pourquoi le Sida se multiplie plus vite chez les personnes tuberculeuses » (in french)
- MediaCités, article published on April 5th, 2019 : « Toulouse: une avancée majeure dans la recherche sur les co-infections tuberculose et Sida » (in french)
- CNRS in South America (in french)